Autoimmune diseases are thought to result from a breakdown in control of the immune system and its inherent tolerance to self antigens. There are several different autoimmune diseases and they affect millions of people worldwide. One or more tissues of the body is generally attacked by the immune system in autoimmune diseases. For example, in multiple sclerosis (MS), myasthenia gravis and autoimmune ureitis, the nervous system is attacked. In Crohn's disease and ulcerative colitis, the gastrointestinal system is attacked, and in psoriasis, pemphigus vulgaris and vitiligo, the skin is affected. Several autoimmune diseases attack multiple organs, for example, systemic lupus erythematosus (SLE), rheumatoid arthritis and scleroderma.
These diseases are characterized by the presence of a multitude of autoreactive antibodies that arise spontaneously. To date, high levels of circulating autoantibodies to DNA are the best evidence of these maladies.
Cross reactivity of antibodies raised in the normal way to a foreign antigen is also a potential source of autoimmune disease, for example, antibodies against streptococcal M protein can cross react with human heart muscle.
Unexplained or idiopathic sensorineural hearing loss (SNHL) is troubling to physicians and patients alike because the etiology is unknown and there are few effective treatments. Autoimmunity is suspected to be a cause of some cases of sudden onset, rapidly progressive or fluctuating hearing loss, particularly when bilateral involvement occurs. Autoimmune sensorineural hearing loss (AISNHL) in humans has been suspected in systemic autoimmune diseases, and there are indications that inner ear organ-specific autoimmunity is involved in rapidly progressive hearing loss (Harris J P (1993 In: 2nd edition, Otolaryngology Head and Neck Surgery, Vol IV: Ear and Cranial Base (Cummings C W, Krause C J, Schuller D E, Fredrickson J M, Harker L A (eds), Mosby Yearbook, St. Louis, Mo.) pp. 2926-2942; McCabe B F (1979) Ann. Otol. 88:585-859; McCabe B F (1991) In: Bearing Of Basic Research On Clinical Otolaryngology, Adv. Otorhinolaryngol (Pfaltz C R, Arnold W, Kleinsasser O (eds), Karger Publishing, Basel, Switzerland, Vol. 46) pp. 78-81; Hughes et al (1988) Laryngoscope 98:251-253; Harris and Ryan (1984) Am. J. Otolaryngol. 5:418-425; Cruz et al. (1990) Am. J. Otol. 11:342-346; Harris (1983) Otolaryngol Head Neck Surg. 91:17; Arnold et al. (1985) Acta Otolaryngol 99:437; Harris and Sharp (1990) Laryngoscope 100:516-524; Moscicki et al. (1994) JAMA 272:611-616; Sismanis et al. (1997) Otolaryngol Head Neck Surg. 116:146-152).
Given the high frequency of idiopathic SNHL, the ability to accurately diagnose AISNHL would be of value since this is one of the few potentially treatable causes of SNHL. However, since treatment of autoimmune disease involves toxic drugs such as corticosteroids, cyclophosphamide, methotrexate and cyclosporin A, all of which have significant side effects, most physicians are reluctant to use these agents without a clear indication (Sismanis et al. (1997) Otolaryngol Head Neck Surg. 116:146-152). Treatment of suspected autoimmune hearing loss is complicated, because without treatment there is a high frequency of spontaneous remission, but in cases that don't regress, the hearing loss may become worse and permanent. Immune-mediated hearing loss also may include 30-50% of Meniere's disease (episodic vertigo and fluctuating progressive hearing loss) patients (Rauch et al (1995) Am. J. Otology 16:648-652; Shin et al. (1997) Laryngoscope 107:222-227).
Early approaches to detecting AISNHL employed cellular assays of immune reactivity, such as lymphocyte transformation and lymphocyte migration inhibition assays using crude inner ear antigens (McCabe B F (1991) In: Bearing Of Basic Research On Clinical Otolaryngology, Adv. Otorhinolaryngol (Pfaltz C R, Arnold W, Kleinsasser O (eds), Karger Publishing, Basel, Switzerland) Vol. 46, pp. 78-81; Hughes et al (1984) Laryngoscope 94:758-767). Unfortunately, these assays did not correlate well with response to therapy (Hughes et al. (1984) Laryngoscope 94:758-767; Kanzaki J and O-Uchi T (1983) Acta. Otolaryngol. (suppl.), 393:77-84; Hughes et al. (1988) Laryngoscope 98:251-253; Veldman et al (1984) Laryngoscope 94:501-507). The poor predictability has been explained by a lack of sensitivity and specificity of these assays for identifying organ-specific autoimmune reactivity (Mattox and Lyles (1989) Am. J. Otol. 10:242-247; Mattox and Simmons (1977) Ann. Otol. Rhinol. Laryngol. 86:463-480).
Autoimmune diseases typically cause a great deal of discomfort and pain in the patient. Clearly, there is a need for a rapid, distinctive and accurate assay that is diagnostic for autoimmune diseases (e.g., rheumatoid arthritis or AISNHL). This rapid diagnosis would aid the clinician in properly prescribing an effective therapeutic regimen to alleviate the pain and symptoms associated with the disease. Furthermore, it would be highly beneficial for clinicians to determine apriori which patients are likely to respond to therapeutic treatment (e.g., immunosuppressive therapy), thereby avoiding the risks associated with such therapy in the population of patients unlikely to respond.